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Biomedical subjects

L A Perry

Publications and source records attributed to L A Perry.

At least 55 records · Page 3Linked to original sources

Plasma cortisol and adrenocorticotropin in appropriate and small for gestational age fetuses.

Plasma cortisol and adrenocorticotropin (ACTH) were measured in fetal blood samples obtained by cordocentesis from 61 appropriate for gestational age (AGA) and in 41 small for gestational age (SGA) fetuses at 18-38 weeks gestation. Fetal plasma cortisol (mean 74 nmol/l) did not change but plasma ACTH increased between 18 and 36 weeks gestation and the two were not significantly correlated. Plasma cortisol in cord blood samples after vaginal delivery at term (mean 305 nmol/l) was higher than in samples at elective cesarean section (mean 151 nmol/l), and there was a significant correlation between fetal and maternal levels. The findings suggest that in human fetuses a late gestational rise in plasma cortisol may not be necessary for organ maturation and that the high fetal plasma cortisol in spontaneous labor at term is probably the result rather than the cause of labor. In SGA fetuses, plasma cortisol was higher and ACTH lower than in AGA fetuses, and plasma cortisol was inversely correlated to fetal hypoglycemia, suggesting that in the chronically hypoglycemic SGA fetus the fetal pituitary is under negative inhibition.

Adrenocorticotropic Hormone↗

Ultra rapid blood sampling for the determination of short-term variations in the circulating concentration of oestradiol in man.

Blood was taken from three healthy female and three healthy male volunteers every 20 s for 15 min. The serum level of oestradiol was measured and the pattern of variation assessed by a cusum plot of the sequential data, by autocorrelation of the detrended serial data, and by looking for pulses. In two cases the variation in oestradiol values was greater than that which could be attributed to variation in the assay. Both these subjects showed a significant overall change in values during the sampling period (an increase and a decrease). There was no trend in the remaining four subjects. In two of the six subjects there was significant autocorrelation of detrended sequential levels. Defining a 'pulse' as three times the assay coefficient of variation no more pulses were identified than was expected from random fluctuations. By frequency analysis the two subjects with significant autocorrelation showed periodic fluctuations of approximately 70/h and 9/h respectively. It is apparent that both the rate of sampling and the method of analysis greatly influence the evaluation of pulsatile release of oestradiol.

Adult↗

Development of a direct [125I]radioimmunoassay for serum levels of 17-hydroxyprogesterone.

We describe a direct, rapid, sensitive and highly specific radioimmunoassay for determining serum levels of 17-hydroxyprogesterone. It is based on the use of highly specific sheep antiserum, 125I-labelled tracer, dextran-coated charcoal to separate the antibody bound and free fractions, and sodium salicylate to eliminate interference from endogenous binding proteins in serum. Intra- and interassay coefficients of variation are less than 8% and recovery is satisfactory. Sensitivity is 3.5 fmol per assay tube (0.14 nmol/l). Results correlate closely with those of an established technique using 3H-labelled steroid after initial solvent extraction and column chromatography of samples (y = 1.02x - 0.16; r = 0.998). The values found for serum from normal adult subjects ranged from 1.0 to 12.1 nmol/l while those from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were 1.4-18.4 and 27.3-650 nmol/l, respectively.

17-alpha-Hydroxyprogesterone↗

Evidence for similarity in testosterone levels in haplotype identical brothers.

An analysis of 89 male sibling pairs from multicase rheumatoid arthritis families demonstrated an association between HLA and serum testosterone levels. In sibling pairs that were haplotype identical, the mean inter-pair difference in testosterone level expressed as a log ratio was significantly less than sibling pairs sharing neither haplotype (p = 0.03). This difference was independent of the RA status of the pairs. These results suggest the presence of a gene(s) controlling testosterone levels linked to the Major Histocompatibility Complex (MHC) on chromosome 6. These findings may aid understanding of the roles of HLA antigens and sex hormones in the susceptibility to RA and other autoimmune disease.

Arthritis, Rheumatoid↗

The production and characterisation of antisera to 17-hydroxyprogesterone.

Sheep were immunised with 11-deoxycortisol-21-hemisuccinate-bovine serum albumin (11-deoxycortisol-21-HS-BSA) or with 17-hydroxyprogesterone-7 alpha-carboxyethyl thioether-keyhole limpet haemocyanin (17-OHP-7 alpha-CETE-KLH) or with 17-OHP-3-(O-carboxymethyl)oxime-KLH (17-OHP-3-CMO-KLH). The resultant antisera were assessed using [3H]17-OHP and dextran-coated charcoal to separate the antibody bound and free fractions. All sheep produced antisera with an apparent affinity constant of from 1.4 to 6.6 X 10(9) 1/mol. Those raised against 11-deoxycortisol-21-HS-BSA had titres ranging from 1:12,000 to 1:78,000 but showed significant cross-reactivity with many of the steroids tested. Sheep immunised with 17-OHP-7 alpha-CETE-KLH had antisera titres of from 1:102,000 to 1:180,000 and only 17-hydroxypregnenolone cross-reacted significantly (10-20%). The best antisera were raised in sheep immunised with 17-OHP-3-CMO-KLH. Titres ranged from 1:168,000 to 1:390,000 and there were about 8 g/l of specific antibodies which cross-reacted 5.7% or less with 17-hydroxypregnenolone, and less than 0.5% with progesterone, 11-deoxycortisol and the other steroids studied. The antisera to 17-OHP-3-CMO-KLH were further assessed using [125I]17-OHP; titres ranged from 1:5,700,000 to 1:18,000,000 with affinity constants of from 1.67 to 2.5 X 10(10) 1/mol. They showed minimal or no cross-reactivity with the steroids studied. Reimmunisation after an 8-month interval produced antisera with a higher affinity constant and even lower cross-reactivity with other steroids.

17-alpha-Hydroxyprogesterone↗

Saliva levels of oestradiol and progesterone in relation to non-protein-bound concentrations in blood during late pregnancy.

Serum and saliva samples were obtained from 25 women in the last eight weeks of pregnancy. The concentrations of oestradiol and progesterone were measured by radioimmunoassay. The proportion of each hormone which was not bound to protein in serum was measured by centrifugal ultrafiltration: for progesterone the unbound fraction was 2.5% (2.13--2.78%) and for oestradiol 1.27% (1--1.83%). There was only a weak relationship between the free hormone concentrations estimated in blood and the levels measured in saliva. We conclude that, for the situation examined here, saliva does not provide a useful measure of unbound, biologically active steroid.

Estradiol↗

Androgen suppression by hydrocortisone without aminoglutethimide in orchiectomised men with prostatic cancer.

The effects of hydrocortisone (HC) alone and in combination with aminoglutethimide (AG) have been studied on circulating blood levels of androgens in orchiectomised men with metastatic prostatic cancer. Serum testosterone levels were significantly lower in both early and late hydrocortisone-treated patients compared with pre-treatment levels. The regimen of HC + AG increased serum testosterone almost back to pre-treatment levels. Similar observations were noted with serum androstenedione, dehydroepiandrosterone sulphate and sex hormone binding globulin (SHBG) levels. Clinical responses to hydrocortisone alone have been observed in this series of patients. It is concluded that aminoglutethimide has no place in the therapy of prostatic cancer and that physiological doses of hydrocortisone represent the best second hormonal manoeuvre for prostatic cancer patients.

Aged↗

A relationship between sex hormone binding globulin and dehydroepiandrosterone sulfate in normally menstruating females.

Blood samples were collected from 120 normally menstruating women throughout the menstrual cycle. Serum was assayed for sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2) and testosterone (T). There was an inverse relationship between SHBG and DHEAS, but no relationship between T or E2 and SHBG levels. There is at present no model which readily explains this inverse relationship between SHBG and DHEAS in normal subjects.

Adolescent↗

Early diagnosis of 11 beta-hydroxylase deficiency in two siblings confirmed by analysis of a novel steroid metabolite in newborn urine.

Plasma and urinary steroid measurements are reported in 2 normotensive newborn female siblings with virilized external genitalia due to 11 beta-hydroxylase deficiency. Plasma 11-deoxycortisol concentrations were markedly elevated whereas 17OH-progesterone concentrations were not raised. Plasma renin activity was suppressed, but increased to levels characteristic of infancy within 4 weeks of treatment. The enzyme defect was confirmed by measurement of increased urinary excretion of tetrahydro-11-deoxycortisol. A more polar steroid metabolite, 6 alpha-hydroxytetrahydro-11-deoxycortisol was also determined by gas chromatographic and mass spectrometric analysis. Analysis of metabolites in urine is an additional specific marker to plasma 11-deoxycortisol measurement for the diagnosis of 11 beta-hydroxylase deficiency in early infancy.

17-Hydroxycorticosteroids↗

Placental protein 12 (PP12): a new test for the prediction of the small-for-gestational-age infant.

The circulating levels of placental protein 12 (PP12) and placental lactogen (hPL) were measured in 501 women between 36 and 41 weeks gestation. There was a significant positive association between hPL levels and infant birthweight and a significant negative association in the case of PP12 levels. The clinical efficiency of elevated PP12 levels in the prediction of low-birthweight infant at term compared favourably with that of reduced hPL levels.

Birth Weight↗

Quantitative cytophotometric determination of DNA, RNA and lysine bound protein in relationship to zygote formation and protein synthesis in myxamoebae and swarm cells of Didymium iridis.

Quantitative cytochemical determinations were made of the DNA of zygotes formed from myxamoebae and swarm cells of Didymium iridis. The nuclear and cytoplasmic RNA and lysine bound protein of these cells were also measured. Significant zygote formation in myxamoebae crosses began at 20-30 min, while swarmers required 35-40 min. Myxamoebae, however, demonstrated a greater ability to form zygotes. The total cytoplasmic RNA and protein bound lysine for myxamoebae was higher than that of the swarmer cells. This observed decrease in swarmers may be due to reduced protein synthesis. Values for nuclear RNA were higher in the myxamoebae, but nuclear lysine bound protein was higher in the swarmers. The data presented suggest that prefusion swarmers, after replicating their DNA, go into a period of G2 arrest and remain in this condition postfusion. In contrast, prefusion myxamoebae readily divide after DNA replication, and continue to synthesize nuclear DNA, and to divide after fusion.

Crosses, Genetic↗

Polarization fluoroimmunoassay of 11-deoxycortisol in serum and saliva.

We developed polarization fluoroimmunoassays for 11-deoxycortisol in serum and saliva. To avoid interfering factors, the steroid was initially extracted from the biological fluids with dichloromethane. Assays could then be completed without any further separation procedures or need to correct for blank signals. The serum assay was suitable for following the response to the metyrapone test and results correlated acceptably with those by an established, specific, direct 125I-radioimmunoassay. The method is not sufficiently sensitive to detect 11-deoxycortisol in normal saliva, but greatly increased concentrations were found in post-metyrapone saliva and results agreed well with those by the radioimmunoassay as modified for salivary assay. Salivary 11-deoxycortisol assay would provide a convenient means of monitoring results of the metyrapone test.

17-Hydroxycorticosteroids↗

A direct radioimmunoassay for 11-deoxycortisol.

A rapid, sensitive and highly specific radioimmunoassay (RIA) for 11-deoxycortisol has been developed and used for the measurement of serum concentrations. Antisera were raised using 11-deoxycortisol -3-carboxymethyloxime-bovine serum albumin as immunogen and showed minimal cross reaction with related steroids. 11-Deoxycortisol-3-carboxymethyloxime was coupled to 125 I-iodohistamine to produce a labelled antigen of high specific activity (s.a. 680 Ci/mmol). The assay was performed for 1h at room temperature and pH 4. Results were correlated with those after extraction, high pressure liquid chromatography and RIA of serum samples (y= 0.78x + 36.9; r = 0.97, p less than 0.001). The accuracy of the method was satisfactory (y = 1.00x - 0.61; r= 0.95; p less than 0.001). Assay sensitivity was 0.3 nmol/l. 11-Deoxycortisol concentrations in normal subjects at 09.OOh were 26-46 nmol/l (37.2 +/- 5.7; x- +/- 1 S.D.). The assay should facilitate the investigation of patients with possible abnormalities of adrenocortical function.

17-Hydroxycorticosteroids↗